Dissecting π-helices: Sequence, structure and function

Abstract

A new procedure for the identification of regular secondary structures using a Cα trace has identified 659 π-helices in 3582 protein chains, solved at high resolution. Taking advantage of this significantly expanded database of π-helices, we have analysed the functional and structural roles of π-helices and determined the position-wise amino acid propensity within and around them. These helices range from 5 to 18 residues in length with the average twist and rise being 85.2 ± 7.2 and 1.28 ± 0.31 Å, respectively. A total of 546 (~ 83%) out of 659 π-helices occur in conjunction with α-helices, with 101 π-helices being interspersed between two α-helices. The majority of interspersed π-helices were found to be conserved across a large number of structures within a protein family and produce a significant bend in the overall helical segment as well as local distortions in the neighbouring α-helices. The presence of a π-helical fragment leads to appropriate orientation of the constituent residues, so as to facilitate favourable interactions and also help in proper folding of the protein chain. In addition to intra helical 6→1 N-H···O hydrogen bonds, π-helices are also stabilized by several other non-bonded interactions. π-Helices show distinct positional residue preferences, which are different from those of α-helices. π-helices are more common than generally believed and show certain positional residue preferences, which are different from those of α-helices. Residue propensity in π-helices is context dependent and influences the residues occurring in preceding and following α-helices. π-helices help in correctly orienting certain critical residues for proper interactions and interspersed π-helices are generally conserved across large number of structures in a family.